Group-sequential three-arm noninferiority clinical trial designs

J Biopharm Stat. 2017;27(1):1-24. doi: 10.1080/10543406.2016.1148710. Epub 2016 Feb 18.

Abstract

We discuss group-sequential three-arm noninferiority clinical trial designs that include active and placebo controls for evaluating both assay sensitivity and noninferiority. We extend two existing approaches, the fixed margin and fraction approaches, into a group-sequential setting with two decision-making frameworks. We investigate the operating characteristics including power, Type I error rate, maximum, and expected sample sizes, as design factors vary. In addition, we discuss sample size recalculation and its impact on the power and Type I error rate via a simulation study.

Keywords: Assay sensitivity; Cui-Hung-Wang statistics; Type I error; average sample number; fixed margin approach; fraction approach; maximum sample size; sample size recalculation.

MeSH terms

  • Equivalence Trials as Topic*
  • Humans
  • Research Design*
  • Sample Size